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  3. Lung Disease Lookup
  4. Lung Cancer
  5. Symptoms & Diagnosis
  6. Biomarker Testing
  7. EGFR
  8. EGFR Exon 20 Insertion Mutation

EGFR Exon 20 Insertion Mutation and Lung Cancer

Testing for EGFR exon 20 insertions helps your doctor understand your lung cancer and recommend treatments that may work better for you.

EGFR Exon 20 at a Glance:

  • EGFR exon 20 insertion mutation is a type of lung cancer biomarker. 
  • Patients who test positive for an EGFR mutation may have an exon 20 insertion mutation. 
  • The mutation is more often found in people who never smoked and in Asian populations.

Frequently Asked Questions about Biomarker Testing
Exon 20 patient representation The true frequency of EGFR exon 20 insertion mutations in non-small cell lung cancer (NSCLC) is unknown, but likely ranges from 1-10%, with 3-4% being most commonly reported.

What Is an Exon 20 Insertion Mutation?

EGFR exon 20 insertions are one type of lung cancer biomarker. They are a type of EGFR mutation that leads to uncontrolled cell growth and development of cancer. 

Exon 20 DNA Changes in this biomarker can cause cancer cells to grow or spread.

Why Biomarker Testing Matters

  • Ensures precision treatment, not trial‑and‑error
  • Opens access to FDA‑approved targeted drugs and clinical trials
  • Helps clinicians plan the most effective first‑line and subsequent therapies
  • Supports better outcomes and quality of life
Biomarker testing looks for specific genetic changes in the tumor to help guide treatment. Testing includes DNA-based tests to identify changes in the genes themselves, and RNA-based tests to measure how those genes behave, giving your care team a fuller picture of your tumor makeup and available treatment options.

How Is Testing Done for Exon 20 Insertions?

Testing is usually done at diagnosis or when treatment changes. Your doctor will need to test your tumor through a tissue or blood (liquid) biopsy. There are several different types of tests that doctors use to look for changes, or biomarkers in your cells:

  • Fluorescence in Situ Hybridization, or FISH, analysis is a common genetic test. FISH analysis looks at changes in the chromosomes through tissue under a microscope.
  • Immunohistochemistry (IHC) looks for proteins in the cell under a microscope.
  • Next-generation sequencing (NGS), also called comprehensive biomarker testing, is when tissue from a patient's tumor (gathered from a biopsy) is placed in a machine that looks for many possible biomarkers at one time.
  • Reverse transcription polymerase chain reaction (RT-PCR) is a laboratory method used to make many copies of a specific genetic sequence for analysis.

Your doctor may perform several of these tests at the same time to help confirm results. Different biomarkers rely more heavily on certain tests.

Testing for EGFR exon 20 insertions is usually done with next‑generation sequencing (NGS) or PCR‑based tests, which look for specific changes in the EGFR gene. These tests can identify exon 20 insertions that differ from more common EGFR mutations and may require different treatment approaches. Liquid biopsy can sometimes detect EGFR exon 20 insertions when tissue is limited, but tissue‑based NGS provides the most complete information. 

Learn more about the different types of biomarker tests. 

Understanding Your Exon 20 Insertion Test Results

Chemotherapy and targeted treatment therapies are available.

Other biomarkers may guide treatment. If a new or different biomarker has been identified, your doctor will recommend a targeted therapy to treat that biomarker.

Additional or repeat testing may be needed, especially if the cancer grows after treatment. 

How EGFR Exon 20 Results Influence Treatment

An EGFR exon 20 insertion result can help guide treatment decisions. 

Exon 20 insertion mutations are resistant to standard EGFR tyrosine kinase inhibitors (TKIs), which are drugs that are used to block cancer growth.

If you are diagnosed with the EGFR exon 20 mutation, your first-line treatment option will likely include chemotherapy with amivantamab (Rybrevant), a type of targeted therapy called a monoclonal antibody. 

Sunvozertinib (Zegfrovy) is also an FDA-approved treatment for EGFR exon 20 insertion NSCLC post-platinum chemotherapy (approved in July 2025).

If your cancer grows after treatment, you should get another biopsy to see if a different biomarker has developed. If a new biomarker has been identified, your doctor will recommend a targeted therapy to treat that biomarker. 

If no new biomarker is found, your doctor may recommend one of the following options: 

  • Chemotherapy alone or with amivantamab (if you haven’t already received it)
  • Chemotherapy with another monoclonal antibody called bevacizumab (Avastin) 
  • Immunotherapy

All lung cancer patients should ask their doctors if they are eligible to participate in a clinical trial.

Questions to Ask Your Doctor

Work with your doctor to discuss your goals and options each time you have to review and interpret test results to make a treatment decision. The three big questions to ask are:

  • What is the goal of this treatment?
  • What are the potential side effects?
  • What other options do I have?

Research is happening at a rapid pace, and your doctor should be up to date on the recommendations for your specific type of lung cancer. If you don’t feel comfortable with the answers you are receiving, do not hesitate to seek out a second opinion.

What to Do After an Exon 20 Insertion Diagnosis

Someone with an EGFR exon 20 insertion–positive lung cancer diagnosis can take several empowering steps to stay ahead of their care. These are general medical information steps, not personal medical directives, and it’s important to work closely with a qualified healthcare professional for decisions about diagnosis or treatment. 

EGFR Exon 20 insertions include several variants, and knowing the exact insertion can help your care team determine whether targeted therapies or clinical trials may be appropriate. 

Next‑generation sequencing (NGS) can identify EGFR Exon 20 insertions along with other biomarkers (such as PD‑L1, MET, HER2, KRAS, ALK) that may influence treatment decisions or eligibility for targeted options. 

If tissue was limited or if more information is needed later, a blood‑based ctDNA test may detect EGFR Exon 20 insertions or emerging resistance mutations as treatment progresses. 

EGFR Exon 20 insertions are recognized as a distinct biomarker in non‑small cell lung cancer, and guidelines outline when targeted therapies or clinical trials may be considered. 

Having your reports available helps you track what has already been tested, understand your mutation profile, and avoid delays if you seek a second opinion or explore clinical trial options. 

Support and Patient Experiences

Whether you're newly diagnosed or navigating treatment, support resources and patient experiences can help you better understand your options and connect with others.

Connect with Support Resources

View the EGFR Exon 20 Infographic (PDF)

Hear from Other Patients

Hear Carla's inspiring story of how a biomarker test identified her EGFR exon 20 insertion mutation and led to targeted therapy options. 

Carla G shares more on her lung cancer journey with an EGFR Exon 20 Insertion.

Video transcript

Lung cancer research can move at a rapid pace. Always speak with your doctor about the most up-to-date treatment guidelines.

Medically reviewed by: Jorge Gomez, MD

Last reviewed: June, 2026 

Page last updated: August 19, 2026

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